The major portion of this research will involve an extensive, quantitative investigation of the importance of intercellular matrix structures to contractile properties of and ionic movements within normal and hypertrophied myocardium. Previous observations have noted that the amount of collagen, a major element of the intercellular matrix, which appears in hypertrophic tissue depends upon the hypertrophic stimulus and that this collagen alters contractile function. Recent observations suggest that glycoproteins on cell membrane surfaces, also prominent elements of the intercellular matrix, influence the tissue movements of many substances, including calcium. These glycoproteins, especially those of fibroblasts, would be expected to increase in hypertrophy, particularly that hypertrophy characterized by prominent connective tissue (CT) proliferation and may also alter contractile function. This research will induce hypertrophy in a baseline series of rabbit hearts with isoproterenol and with thyroxine, stimuli which promote large and small amounts of CI proliferation respectively. The contractile function, tissue calcium movements, water contents, and extracellular space will be quantitated in each type of hypertrophy. Identical studies will be conducted in a second series of rabbit hearts in which CT proliferation is inhibited by BAPN and in a third series in which a fibroblast membrane glycoprotein (fibronectin) is inhibited by tunicamycin. A fourth series will be studied in which both collagen and fibronectin are inhibited. The minor portion of this research is based on the observation that diazepam directly and selectively inhibits synthesis of myosin heavy chains in cell culture. Diazepam will be administered to rabbits during development of pressure overload hypertrophy and the contractile function of their hearts will subsequently be tested to determine whether diazepam interfers with normal compensatory processes.